The long term goal of the candidate is to understand the physiologic and pathophysiologic mechanisms of host-microbial interactions. The candidate hypothesizes that commensal and probiotic biofilms in the colonic mucosa act as a prominent stimulus for epithelial cell development and differentiation, and that cross-talk among bacteria, and between bacteria and epithelium provide fundamental signaling in gut physiology. All mammals, including humans, are adapted to life in a microbial world and are colonized by bacteria on all their body surfaces at birth. The stimulation of commensal bacterial antigens is crucial for the normal development of the mucosal immune system and the maintenance of tolerance. In fact, animals that are kept germ-free from birth have dysfunctional immune systems, their development is somehow stunted and their energy requirements are abnormally elevated. This study will attempt to define some of the aspects of bacteria-induced intestinal epithelial cell differentiation in a reductionist and an in vivo model challenged with distinct strains of commensal and probiotic. The specific aims proposed are to investigate: 1. Role of commensals and probiotics in modulating the homeostasis of the colon: 2. Role of commensals and probiotics in modulating intestinal epithelial cell inflammatory responses. These studies will be performed using human intestinal epithelial cell lines in vitro and human fetal intestine xenografts in SCID mice ex vivo, and will be carried out applying electrophysiological methods, protein analysis, immunohistochemistry and DNA microarray analysis.